Conventional rats fed a chemically defined amino acid liquid diet (J2) developed anemia, azotemia and pancreatic acinar atrophy and fibrosis. The basis for the hemolytic anemia is a defect in the red blood cells. The abnormalities developed to a much less extent in germ- free rats fed this same liquid diet, or in conventional rats fed the ingredients of this liquid diet in solid form, or in rats fed other liquid diets of similar chemical composition. Feeding bovine serum albumin, alpha-lactalsumin, casein or casein hydrolysate as solid supplements to the liquid diet prevented or cured the anemia and ameliorated the pancreatic lesion, but feeding a supplement of amino acids in amounts and proportions similar to the composition of casein had no prophalactic or therapeutic effects. No vitamin, alone or in combination with other vitamins, had any prophylactic or therpeutic effects. We have shown that cysteine ethyl ester is critically involved in inducing the pathologic syndrome but that its effects are conditioned by a number of dietary (chemical and physical) and host factors (including the indigenous microflora). The main objectives of our studies are: (1) to define the pathogenesis of the syndrome, with particular emphasis on how the above mentioned dietary chemical (especially cysteine ethyl ester and other amino acids) and host microbial factors interact to produce the hemolytic anemia, azotemia, and pancreatic acinar atrophy and fibrosis; (2) to determine the nature of the red blood cell defect and hemoglobin abnormality in the anemic rats; (3) to determine the component of the proteins and casein hydrolysate which is protective. Techniques of experimental nutrition, biochemistry, organic chemistry, and hematology are used. (4) A long term goal is to relate the findings of this research to humans in health and disease especially pancreatic disorders and nutritional anemias, and the practices of human nutrition and therapy.